Lab Notes: Disarming Darth Vader

Removing virulence factors from pathogenic bacteria could be a new way to fight infections, by taming rather than killing them. Also: thanks to epigenetics, learned behaviors may be inherited.

'Naked Darth Vader' Approach Defangs Bacteria

Canadian researchers have found a bacterial virulence factor that, when removed, made pathogenic Brucella species relatively tame, according to a study in the journal Chemistry & Biology.

The protein VirB8 is a "key part of the virulence mechanism of human and animal Brucella species of bacteria," said lead author Christian Baron, PhD, of the University of Montreal, in a statement.

He compared targeting the protein with the removal of the Star Wars villain Darth Vader's armor and lightsaber, noting that without those tools, the Sith lord would be much easier to attack -- just as bacteria without virulence would essentially be rendered harmless.

Baron and co-authors noted that this alternative treatment route could slow or halt the growing problem of bacterial drug resistance, and that their findings could open new doors to microbial virulence mechanisms.

-- Cole Petrochko

Anxious Mice Breed Anxious Daughters

Mice exposed to social stresses when young exhibit anxiety and disruptions of socialization throughout their lives. And in experiments with stressed male mice, even when mated with unstressed females, the anxiety behaviors were transmitted to female offspring for up to three generations, according to researchers from Tufts University in Boston.

The mice were stressed through chronic social instability by routinely changing their cage mates, resulting in their faring poorly on various behavioral and sociability tests several months later. Similar behaviors were consistently seen in their female pups at 2 months of age, and again in successive generations. "Remarkably," the researchers wrote in Biological Psychiatry, none of the male progeny of stressed mice had these altered behaviors.

The long-lasting multigenerational behavioral disruptions did not appear to be learned. Rather, they resulted from dysregulation of hippocampal Rcan genes – a mode of inheritance previously unrecognized that may have implications for human psychiatric disorders, they suggested.

"Individual risk for psychiatric disorders that involve enhanced anxiety and/or social dysfunction may be dependent not only on the specific alleles of genes that are inherited from one's parents and on one's own experiences, but also on the experiences of one's parents when they were young," they wrote.

-- Nancy Walsh

Niacin Flush Doesn't Improve Lipids

Researchers have long thought that the same mechanism involved in a niacin "flush" was responsible for its beneficial effects on lipids.

But a new study in Science Translational Medicine rules out the GPR109A receptor as niacin's pathway to lower triglycerides and LDL and higher HDL.

It's well established that "flushing" results when niacin activates GPR109A, releasing prostaglandin D2. Researchers have thought this activation was also responsible for a reduction in free fatty acid, ultimately leading to the lipid benefits.

But Andrew Plump, MD, of Merck, and colleagues found that mice lacking GPR109A still gleaned the benefits of improved lipid profiles from niacin. And while humans given either of two GPR109A agonists had acute lowering of free fatty acids, there were no larger effects on serum lipids.

The researchers said it's still not clear how niacin benefits lipid parameters, but it doesn't appear to be mediated by the GPR109A receptor.

-- Kristina Fiore

Friend or Foe? Gut Confused By Infection

A healthy mucosal barrier in the intestines keeps the millions of bacteria there happily breaking down food without being attacked for their services.

But when that barrier breaks down, the immune system attacks both "good" and "bad" bacteria, researchers reported in Science.

In mice with a GI mucosal infection, the immune system stopped tolerating commensal bacteria and started forming pathogen-specific T cell to them that went on to make memory cells that persisted after the infection.

The combination of GI barrier dysfunction and infection has been shown to induce inflammatory bowel disease, which may have bigger implications, as the group noted.

"As bacteria colonize all pathogen entryways, such as the skin, lung and GI tract, our findings raise the question of whether immunity and inflammation at barrier sites is generally controlled by responses to commensals," they wrote.